Role of SIRT6 in the pancreatic beta cell aging

SIRT6在胰腺β细胞衰老中的作用

• 批准号: 10371337
• 负责人: X Charlie Dong
• 金额: $ 23.78万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-15 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10371337
• 关键词: Age; Age-Years; Aging; B Cell Proliferation; B-Cell Development; Beta Cell; Biological Process; Calcium Signaling; Cell Aging; Cell Death; Cell membrane; Cell physiology; DNA Damage; Data; Deacetylase; Defect; Development; Diabetes Mellitus; Diet; Disease; Epigenetic Process; Female; Gene Expression; Gene Expression Regulation; General Population; Genes; Glucose; Glucose Intolerance; Guanosine Triphosphate Phosphohydrolases; HDAC4 gene; Histologic; Homeostasis; Human; Impairment; Insulin; Intervention; Islets of Langerhans; Knock-out; Knockout Mice; Knowledge; Life; Literature; Longevity; Metabolic; Metabolism; Mission; Mitochondria; Modeling; Molecular and Cellular Biology; Monitor; Monomeric GTP-Binding Proteins; Mus; Non-Insulin-Dependent Diabetes Mellitus; Oxidative Stress; Persons; Phenotype; Physiological; Physiology; Play; Population; Premature Mortality; Prevalence; Prevention; Process; Proteins; Public Health; Regulation; Research; Risk Factors; Role; Sirtuins; Structure of beta Cell of islet; Testing; Transgenes; Transgenic Mice; United States National Institutes of Health; age related; anti aging; base; blood glucose regulation; burden of illness; cell age; cell injury; diabetes pathogenesis; epigenetic regulation; expectation; gene function; glucose metabolism; high risk; human old age (65+); improved; innovation; insight; insulin secretion; male; middle age; molecular phenotype; mouse model; new therapeutic target; novel; overexpression; therapeutic development; transgene expression; voltage

Project Summary During aging, pancreatic beta cells undergo a decline in insulin secretion capacity, and this contributes to nearly 3-fold high diabetes prevalence in people aged over 65 years compared to the general population. Sirtuin 6 (SIRT6), a histone deacetylase, has been suggested to be a longevity factor. In the preliminary study, we have demonstrated that SIRT6 is required to maintain normal beta cell function and SIRT6 is downregulated in the beta cells during aging. Therefore, we hypothesize that SIRT6 plays an important role in the protection of pancreatic beta cells against aging-associated cellular damage. In this application, we will investigate the SIRT6 function and mechanism in the regulation of pancreatic beta cell aging. It is our expectation that the findings from this project will advance our understanding of the fundamental process of the aging of pancreatic beta cells and provide potential novel targets for the development of prevention and treatment of the age-related diabetes.

项目摘要 在衰老过程中，胰腺β细胞的胰岛素分泌能力下降， 导致65岁以上人群的糖尿病患病率是 一般人口。Sirtuin 6（SIRT6）是一种组蛋白脱乙酰酶，被认为是一种长寿因子。 在初步研究中，我们已经证明SIRT6是维持正常β细胞所必需的。 在衰老过程中，β细胞中的SIRT6功能下调。因此，我们假设SIRT6 在保护胰腺β细胞对抗衰老相关的细胞凋亡中起重要作用。 损害在本申请中，我们将研究SIRT6在调节细胞凋亡中的功能和机制。 胰腺β细胞老化我们期望，该项目的发现将推动我们的 了解胰腺β细胞老化的基本过程，并提供潜在的 开发预防和治疗年龄相关糖尿病的新靶点。